Factors Regulating The Temporal And Spatial Assembly Of G-protein Coupled Receptor-mediated Arrestin Complexes
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicatin ....G-protein coupled receptors are proteins that are present at the surface of most cells in the human body. They recognise and bind to specific molecules, such as hormones, the act of which results in a specific signal being transmitted into the cell. This signal alters the function of the cell and so it is critical that it is appropriate, both in type and duration. G-protein coupled receptors and the molecules that activate them provide an essential function within the human body for communicating between cells, and consequently between organs. They are a major mechanism by which nerve signals are transmitted and hormones regulate bodily functions. They are therefore an important target for pharmaceuticals, with up to 50% of ethical drugs and many drugs of abuse acting upon them. It is critical to understand how these receptors alter cellular function once they receive an appropriate signal, but it is also essential to know how such responses are switched off. Arrestins are proteins within cells that interact with G-protein coupled receptors to 'arrest' their signalling. They desensitise the cell to continuous stimulation, but also act to resensitise the cell to respond to future, separate signals. Recently, they have also been shown to provide alternative mechanisms of altering cellular activity by interacting with other cellular proteins. These interactions greatly increase the potential ways in which a cell can respond once a G-protein coupled receptor is activated. Understanding the resulting complexity is essential if we are to fully exploit the vast therapeutic potential of this important receptor family.Read moreRead less
Determinants Of Tissue- And Ligand-Specific Responses At The Mineralocorticoid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$668,485.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.